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Background: Hepatitis C virus (HCV) is an enveloped and positive-stranded RNA virus that is a major causative agent of chronic liver diseases worldwide. HCV has become the main cause of liver transplantations and there is no effective drug for all hepatitis genotypes. Elucidation of life cycle and nonstructural proteins of HCV involved in viral replication are the attractive targets for the development of antiviral drugs. Methods: In this work, pharmacoinformatics approaches coupled with docking analyses were applied on HCV nonstructural proteins to identify the novel potential hits and HCV drugs. Molecular docking analyses were carried out on HCV approved drugs followed by the ligand-based pharmacophore generation to screen the antiviral libraries for novel potential hits. Results: Virtual screening technique has made known the top-ranked five novel compounds (ZINC00607900, ZINC03635748, ZINC03875543, ZINC04097464, and ZINC12503102) along with the least binding energy (-8.0 kcal/mol, -6.1 kcal/mol, -7.5 kcal/mol, -7.4 kcal/mol, and -7.3 kcal/mol respectively) and stability with non-structural proteins target. Conclusion: These promising hits exhibited better absorption and ADMET properties as compared to the selected drug molecules. These potential compounds extracted from in silico approach may be significant in drug design and development against Hepatitis and other liver diseases.

The aim of present research work was to evaluate the Salvia macrosiphon Boiss. of Lamiaceae (mint family), using biochemical and biological assays. Plant's phytochemicals extraction was performed in methanol, butanol and water by mechanical shaking process. TPC and TFC were determined by Folin-Ciocalteu and aluminum chloride colorimetric procedures, respectively. The highest TPC (99.61±3.45 mg GAE/g) and TFC (234.72±7.12mg CE/g) were obtained in butanol and methanol, respectively. Regarding the antioxidant potential methanol extract showed the highest DPPH° scavenging potential (78.0±2.0%) and reducing activity (0.923±0.020 absorbance). The antibacterial activity of butanol extract against P. aeruginosa were found highest (ZOI = 23±2.00 mm). Antifungal study of methanol extract showed the ZOI (11 ±0.67mm) against F. brachygibbosum. The results revealed that the methanol stem extract of S. macrosiphon bear significant medicinal value and could be used for formulating phytomedicines and food preservers.

BACKGROUND: Excessive inflammation triggered by a hitherto undescribed mechanism is a hallmark of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and is associated with enhanced pathogenicity and mortality. OBJECTIVE: Complement hyperactivation promotes lung injury and was observed in patients suffering from Middle East respiratory syndrome-related coronavirus, SARS-CoV-1, and SARS-CoV-2 infections. Therefore, we investigated the very first interactions of primary human airway epithelial cells on exposure to SARS-CoV-2 in terms of complement component 3 (C3)-mediated effects. METHODS: For this, we used highly differentiated primary human 3-dimensional tissue models infected with SARS-CoV-2 patient isolates. On infection, viral load, viral infectivity, intracellular complement activation, inflammatory mechanisms, and tissue destruction were analyzed by real-time RT-PCR, high content screening, plaque assays, luminex analyses, and transepithelial electrical resistance measurements. RESULTS: Here, we show that primary normal human bronchial and small airway epithelial cells respond to SARS-CoV-2 infection by an inflated local C3 mobilization. SARS-CoV-2 infection resulted in exaggerated intracellular complement activation and destruction of the epithelial integrity in monolayer cultures of primary human airway cells and highly differentiated, pseudostratified, mucus-producing, ciliated respiratory tissue models. SARS-CoV-2-infected 3-dimensional cultures secreted significantly higher levels of C3a and the proinflammatory cytokines IL-6, monocyte chemoattractant protein 1, IL-1α, and RANTES. CONCLUSIONS: Crucially, we illustrate here for the first time that targeting the anaphylotoxin receptors C3a receptor and C5a receptor in nonimmune respiratory cells can prevent intrinsic lung inflammation and tissue damage. This opens up the exciting possibility in the treatment of COVID-19.

COVID-19 now spreading in Pakistan, massive consequences to health and livelihoods are feared as lockdown impacted the food basket and triggered logistics and harvest crisis especially in Punjab and Sindh. Millions of farmers are at the edge of disaster due to shortage of means of transportation, absence of labor force and threat of COVID-19 transmission. We addressed the impact of lockdown on wheat harvesting season in Pakistan and food prices post-COVID-19 outbreak and agriculture supply chain management of vegetables, fruits and pulses. As reported cases increasing in agricultural bread baskets of Pakistan (Punjab and Sindh) in which approximately 70% of harvest of wheat depend on traditional farm laborers, who came from low-income and remote zones before the harvesting period. But this time due to prolonged and partial lock down in all remote and industrial zones of country they could not make it the right profit of the year. The Government announced finical support packages and partially lifted the ban on movement of carriage and equipment for harvesting, but the announcement packages shown to be not as much of useful because most of our machinery needs maintenances and repairing every year around the harvest season and the workshops continued in state of shutdown. It is imperative to keep an eye on the food situation in the country in the middle of this pandemic because keeping supply chains functioning well is crucial to food security. It should be noted that 2 to 3 million deaths in the Bengal famine of 1943 were due to food supply disruptions - not a lack of food availability. There have been information’s of certain anxiety and panic purchasing and interruptions in logistics. It is recommended that to safeguard food security and to reduce the impact of the lockdown, we need to review food policy and analyze how market forces will respond to the imbalanced supply and demand, storage facilities and capacity, price control of products.

Sesame (Sesamum indicum L.) commonly known as 'til' is the most ancient and widely grown oilseed crop of Pakistan. During 2020, field survey conducted in various research fields of Faisalabad (31°26'00.2″N, 73°04'25.4″E) revealed the occurrence of characteristic leaf blight disease with an incidence of 10 to 13%. The symptoms were characterized by yellow-brown and irregular lesions. At later stages, the lesions expanded and the affected leaves turned grayish to dark-brown and finally became wilted. Symptomatic leaves (both the diseased and healthy tissue) were cut into approximately 2 × 2 mm pieces, surface sterilized with 1% sodium hypochlorite for 30 s, 70% ethanol for 30 s, and finally, three times in sterile distilled water prior to culturing on Potato Dextrose Agar (PDA) and incubated at 25 °C under a 12-h photoperiod for 7 days. To obtain pure cultures, hyphal tips of growing mycelia from leaf tissues were carefully isolated and transferred onto fresh PDA plates. Fungal colonies of 11 isolates were initially white, becoming light to dark-gray. The conidia were black, spherical to subspherical, and single-celled (12 to 14 × 18 to 20 μm) in diameter, which were borne on a hyaline vesicle at the tip of the conidiophore. Further, to identify the pathogen to the species level, genomic DNA was extracted using a modified CTAB protocol described by (Guo et al. 2000). The internal transcribed spacer (ITS) region of the ribosomal DNA and translation elongation factor 1-alpha (TEF1-α) gene were amplified using ITS1/ITS4 (White et al. 1990) and EF1-728F/EF1-986R primer sets (Carbone and Kohn 1999), respectively. The sequences were submitted to GenBank (accession no. MW287214 for ITS and MW325222 for TEF1. The sequences comparison revealed 99% and 100% similarity to multiple sequences of N. sphaerica (GenBank accessions KX834822 and MN995332). On the basis of cultural features, conidial morphology and molecular data, the fungus was identified as Nigrospora sphaerica (Sacc.) Mason (Wang et al. 2017; Chen et al. 2018). To test the pathogenicity, fresh and healthy leaves of ten 6-week-old growth stage sesame plants were spray inoculated with a conidial suspension (105 conidia/ml), collected from a 7-day-old culture on PDA. In addition, 10 plants sprayed with sterile distilled water served as controls. Inoculated plants were covered with polyethylene bags to maintain high humidity and kept at 28°C, and observations were made at regular intervals. After 8-10 days of inoculation, leaves developed blight symptoms similar to those observed on naturally infected leaves, whereas control leaves remained asymptomatic. The pathogen was re-isolated from the inoculated leaves, and its identity was confirmed by morphological and molecular (ITS and TEF1) means, thus fulfilling Koch's postulates. N. sphaerica is distributed on a wide range of hosts and has been reported from different host genera including monocotyledonous and dicotyledonous (Wang et al. 2017). Previously, N. sphaerica has been reported to cause leaf blight of Cunninghamia lanceolata in China (Xu and Liu, 2016). To the best of our knowledge, this is the first report of Nigrospora sphaerica as the causal agent of leaf blight of sesame in Pakistan. Because sesame is an important oilseed crop of Pakistan, appropriate disease management practices should be developed and implemented.

The aim of this study was to investigate the phytochemicals using reverse-phase high pressure liquid chromatography (RP-HPLC), antioxidant, antifungal and antibacterial activities of Seriphidium oliverianum stem extracts. The extraction was carried out by conventional shaking process (CSP) and ultrasonic assisted process (UAP). The highest total phenolic contents (97.85 ± 0.735 mg gallic acid equivalent (GAE)/g sample) and flavonoid contents (188.15 ± 0.53 mg catechin equivalent (CE)/g sample) were found in methanol extract obtained by CSP. Antioxidant activity was investigated using DPPH° scavenging assay and reducing power assay. Methanol extract using UAP showed the highest DPPH° scavenging activity (79.95% ± 1.80%) followed by methanol and butanol extracts obtained through CSP. Moreover, methanol extracts using CSP showed highest reducing activity (1.032 ± 0.0205 absorbance). In-vitro antimicrobial activity was studied using most common infection causing fungal and bacterial strains. Anti-fungal activity of methanol extract using CSP showed the highest zone of inhibition (10.5 mm) against F. avenaceum fungal strain, while aqueous extracts obtained through showed the highest antibacterial activity (22 ± 1.32 mm zone of inhibition) against S. aureus. The results showed that the methanol stem extract of S. oliverianum is a valued candidate for further screening and could be processed for in-vivo infection induced animal trials.

Objective The variant allele of rs3798220 in the apolipoprotein(a) gene ( LPA ) is used to assess the risk for coronary artery disease (CAD) in Europeans, where it is associated with short alleles of the Kringle IV-2 (KIV-2) copy number variation (CNV) and high lipoprotein(a) (Lp(a)) concentrations. No association of rs3798220 with CAD was detected in a GWAS of East Asians. Our study investigated the association of rs3798220 with Lp(a) concentrations and KIV-2 CNV size in non-European populations to explain the missing association of the variant with CAD in Asians. Methods We screened three populations from Africa and seven from Asia by TaqMan Assay for rs3798220 and determined KIV-2 CNV sizes of LPA alleles by pulsed-field gel electrophoresis (PFGE). Additionally, CAD cases from India were analysed. To investigate the phylogenetic origin of rs3798220, 40 LPA alleles from Chinese individuals were separated by PFGE and haplotyped for further SNPs. Results The variant was not found in Africans. Allele frequencies in East and Southeast Asians ranged from 2.9% to 11.6%, and were very low (0.15%) in CAD cases and controls from India. The variant was neither associated with short KIV-2 CNV alleles nor elevated Lp(a) concentrations in Asians. Conclusion Our study shows that rs3798220 is no marker for short KIV-2 CNV alleles and high Lp(a) in East and Southeast Asians, although the haplotype background is shared with Europeans. It appears unlikely that this SNP confers atherogenic potential on its own. Furthermore, this SNP does not explain Lp(a) attributed risk for CAD in Asian Indians.

Lipoprotein (a) [Lp(a)] has attracted the interest of researchers and physicians due to its intriguing properties, including an intragenic multiallelic copy number variation in the LPA gene and the strong association with coronary heart disease (CHD). This review summarizes present knowledge of the structure, function, and genetics of Lp(a) with emphasis on the molecular and population genetics of the Lp(a)/LPA trait, as well as aspects of genetic epidemiology. It highlights the role of genetics in establishing Lp(a) as a risk factor for CHD, but also discusses uncertainties, controversies, and lack of knowledge on several aspects of the genetic Lp(a) trait, not least its function.

Objective— Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. Approach and Results— This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene ( LPA ) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter ( P Conclusions— Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Elevated Lipoprotein(a) (Lp(a)) plasma concentrations are a risk factor for cardiovascular disease in humans, largely controlled by the LPA gene encoding apolipoprotein(a) (apo(a)). Lp(a) is composed of low-density lipoprotein (LDL) and apo(a) and restricted to Catarrhini. A variable number of kringle IV (KIV) domains in LPA lead to a size polymorphism of apo(a) that is inversely correlated with Lp(a) concentrations. Smaller apo(a) isoforms and higher Lp(a) levels in central chimpanzees (Pan troglodytes troglodytes [PTT]) compared to humans from Europe had been reported. We studied apo(a) isoforms and Lp(a) concentrations in 75 western (Pan troglodytes verus [PTV]) and 112 central chimpanzees, and 12 bonobos (Pan paniscus [PPA]), all wild born and living in sanctuaries in Sierra Leone, Republic of the Congo, and DR Congo, respectively, and 116 humans from Gabon. Lp(a) levels were severalfold higher in western than in central chimpanzees (181.0 ± 6.7 mg/dl vs. 56.5 ± 4.3 mg/dl), whereas bonobos showed intermediate levels (134.8 ± 33.4 mg/dl). Apo(a) isoform sizes differed significantly between subspecies (means 20.9 ± 2.2, 22.9 ± 4.4, and 23.8 ± 3.8 KIV repeats in PTV, PTT, and PPA, respectively). However, far higher isoform-associated Lp(a) concentrations for all isoform sizes in western chimpanzees offered the main explanation for the higher overall Lp(a) levels in this subspecies. Human Lp(a) concentrations (mean 47.9 ± 2.8 mg/dl) were similar to those in central chimpanzees despite larger isoforms (mean 27.1 ± 4.9 KIV). Lp(a) and LDL, apoB-100, and total cholesterol levels only correlated in PTV. This remarkable differentiation between chimpanzees from different African habitats and the trait's similarity in humans and chimpanzees from Central Africa poses the question of a possible impact of an environmental factor that has shaped the genetic architecture of LPA. Overall, studies on the cholesterol-containing particles of Lp(a) and LDL in chimpanzees should consider differentiation between subspecies.

We report the synthesis, characterization, biological evaluation and quantitative structure-activity relationship of some Schiff base esters as promising new antitumor, antioxidant and anti-inflammatory agents. The Schiff base esters were synthesized by two synthetic routes using variably substituted hydroxy benzaldehydes with para amino phenol in appreciable yields. All the newly synthesized esters have been characterized by (1)H-NMR,(.13)C-NMR, FT-IR techniques and elemental analysis. The synthesized esters were examined for antioxidant, antitumor and anti-inflammatory potentials through different bioassays and quantitative structure-activity relationship was studied. Bioassays showed encouraging results and indicated that some of these title compounds may have potential for further pharmacological investigations.